Mechanisms of bone metastasis formation

Bone is a common metastatic site for many cancers. Tumor cells located in the bone marrow cavity disturb the natural balance (bone remodelling) established between new bone formation performed by osteoblasts and bone resorption carried out by osteoclasts. Tumor cells produce many factors including growth factors and cytokines (PTHrP, ET-1, BMPs, others...) that stimulate either ostoclast activity leading to osteolytic lesions or osteoblast activity generating osteosclerotic bone metastases. Growth factors released from resorbed bone matrix or throughout osteoblastic bone formation sustain tumor growth. Therefore, bone metastases are the site of vicious cycles wherein tumor growth and bone metabolism sustain each other.